In recent studies from this laboratory the investigator has described defects in both renal concerning ability and urinary acidification following lithium administration to man and rats. Despite widespread use of lithium salts, understanding of the mechanism of these defects and of the renal handling of this ion is limited. We propose a systematic study of the effects of lithium on renal function in a series of related experiments. In the first experiments we will measure the interaction of lithium on in vivo vasopressin stimulated renal medullary adenyl cyclase and 3'5' cyclic AMP by radioimmunoassay of these substances in tissue from lithium polyuric rats. Secondly, the location and severity of the acidification defect will be investigated in the rat and in patients with and without associated defects in urine concentrating ability. It is currently held that lithium is reabsorbed primarily if not entirely in the proximal tubule. In the third set of experiments the fractional excretion of lithium and sodium in the rat will be compared under conditions known to alter the tubular sites and fractional reabsorption of sodium. Fourthly, related therapeutic problems in patients will be studied including 1) treatment of lithium induced diabetes insipidus 2) treatment of lithium intoxication 3) evaluation of lithium as therapy in states of inappropriate secretion of antidiuretic hormone.